The meta-analysis of epidemiological studies suggests there may be a modest increase in the risk of breast/ovarian cancer with the use of ADs, especially SSRIs. Other potential explanatory factors for this finding include the role of depression itself rather than treatment with AD 
, failure to distinguish between short- and long-term exposure, and a failure to examine a possible non-linear dose related response as the mechanism for malignant cell proliferation 
. This bi-phasic phenomenon is characterized by “low-dose stimulation and high-dose inhibition” 
of malignant cell proliferation. Thus, rather than having fewer and less severe side effects, short-term use and/or low dose antidepressants could increase the risk of breast and ovarian cancer in women or exacerbate cancer cell growth in women in the early stages of breast and ovarian cancer. Large scale prospective cohort studies of women using SSRIs are needed in order to determine if ADs cause and/or enhance breast and ovarian tumor growth. Specifying induction time and exposure also will allow future researchers to more accurately assess for dose and duration effects.
The fact that industry affiliations were significantly associated with negative findings regarding cancer risk raises public health and policy issues because there is increasing evidence that financial ties among industry, investigators, and academic institutions can affect the research process 
. For example, re-evaluations of liver tissue of rats exposed to dioxin resulted in different conclusions about the liver cancer rates in those rats; industry sponsored reevaluations were associated with fewer cancer characterizations 
, which had an effect on the policy recommendations. Thus, financial associations between biomedical researchers and the pharmaceutical industry may result in the publication of incomplete or inaccurate results and imbalanced recommendations 
. This is not to suggest that researchers with financial associations to industry intentionally designed studies to produce results favorable to manufacturers of ADs or that they misrepresented their results. The existence of researchers' industry associations points to a generic
that a financial conflict of interest may compromise the research process or undermine public trust; “conflict[s] of interest do not imply that any [specific researcher] is improperly motivated.” As Thompson, 2009, astutely notes, it is virtually impossible to determine that a particular decision during the research process was motivated by secondary interests (e.g., financial gain). Although space precludes a more extensive discussion, we agree with Thompson 
that the generic risk incurred by financial conflicts of interest undermines public trust. “[T]he point is to minimize or eliminate circumstances that would cause reasonable persons to suspect that professional judgment has been improperly influenced, whether or not it has
(emphasis added)” [91, p137]
. Thus, we need to develop mechanisms and policies that enhance public trust in the biomedical field (e.g., by creating ‘firewalls’ between industry and academic researchers).
Moreover, there are many posited mechanisms for the link between conclusions and industry ties—mechanisms that can be subtle and unintentional. Our current regulatory system does not incentivize industry to develop maximally informative study designs 
, which may in turn reinforce implicit bias. For example, industry affiliated researchers are incentivized to design pre-clinical studies that use only those dosages that have been associated with antiproliferative effects. Our findings suggest that there is a need to either incentivize industry to use non-linear dose response models or change carcinogenicity guidelines (outlined below).
Given the lack of epidemiological data on low-dose SSRI use, the issue of informed consent becomes a complex and critical one. It is likely that women, especially women being prescribed adjunctive AD therapy for depression secondary to a breast or ovarian cancer diagnosis or as adjunctive therapy for pain and hot flashes, would want to know about the positive cancer findings of animal and human studies, the genotoxic properties of some ADs, as well as the potential neoplastic/antiproliferative findings reported in some studies. Additionally, our findings have implications in light of the latest U.S. Preventive Services Task Force (USPSTF) guidelines recommending that women between the ages of 40–49 do not need routine screening for breast cancer 
. Non-high risk women between the ages of 40 and 49 who have taken ADs, especially low dose SSRIs, may want to continue to get yearly mammograms. Also, although some regulatory agencies suggest that researchers consider using middle and low doses for rodent carcinogenicity studies (e.g., the FDA), we recommend that agencies require researchers to use non-linear dose response models when assessing the carcinogenicity of drugs.
Our study has several limitations. First, some of the articles retrieved were published prior to the development of COI policies and standard disclosure practices. It is likely that our screening techniques missed some industry ties and disclosure depends upon honest reporting of those ties. Thus, our findings should be considered de-minimis
figures. Second, although we searched multiple databases, we did not search EMBASE. However, in light of the documented retrieval congruence between MEDLINE and EMBASE 
and the fact that we hand-reviewed the reference sections of most of the articles that met study criteria, it is unlikely that we would have missed a significant number of articles that would have changed our study results. However, future researchers should include EMBASE to ensure as complete a search as possible. Third, although a random-effects meta-analysis was conducted, results should be interpreted with caution given that the studies included were very heterogeneous in terms of – amongst others – design, patient population, outcomes measured, and follow-up times. Moreover, too few studies were available to conduct meaningful subgroup analyses accounting for some of these characteristics. Future research should include a systematic review of all epidemiological data on cancer risk and AD use. Progress in the field of pharmacogenomics has led to increasing concerns about the complex relationships among serotonin, SSRIs, certain TCAs, prolactin, and tamoxifen, and how these inter-relationships affect pharmacodynamics and cancer risk 
. It is recommended that future research examine this body of literature and investigate the association between industry funding and qualitative conclusions regarding cancer risk.